Hydrothiolation processes such as the thiol-ene reaction have been known for over a century (Dondoni (2008) Angew. Chem. Int. Ed. 47:8995-8997; Posner (1905) Ber. Deut. Chem. Ges. 38:646-657). Because these reactions proceed via radical intermediates, anti-Markovnikov selectivity is usually observed. However, obtaining Markovnikov addition products still represents a significant challenge. Transition metal-promoted hydrothiolations of unactivated alkynes are known (Weiss, et al. (2009) J. Am. Chem. Soc. 131:2062-2063; Cao, et al. (2005) J. Am. Chem. Soc. 127:17614-17615; Ananikov, et al. (2005) Adv. Synth. Catal. 347:1993-2001; Kondoh, et al. (2005) J. Org. Chem. 70:6468-6473; Kondoh, et al. (2007) Org. Lett. 9:1383-1385; Malyshev, et al. (2006) Organometallics 25:4462-4470), but are relatively rare because sulfur can often act as a poison for these catalysts (Kondo & Mitsudo (2000) Chem. Rev. 100:3205-3220). Even fewer reports of the corresponding hydrothiolation of unactivated alkenes have been described. These systems are stoichiometric in metal (Belley & Zamboni (1989) J. Org. Chem. 54:1230-1232; Mukaiyama, et al. (1973) Chem. Lett. pg. 355-356), require the use of very strong protic acids (Screttas, et al. (1979) J. Org. Chem. 44:713-719), or Montmorillonite K-10 clay (Kanagasabapathy, et al. (2001) Tetrahedron Lett. 42:3791-3794). A catalytic system in which a Lewis acid was able to promote the hydrothiolation of an alkene has been described (Weïwer & Duñach (2006) Tetrahedron Lett. 47:287-289; Weïwer, et al. (2006) Chem. Commun. pg. 332-334; Weïwer, et al. (2007) Eur. J. Org. Chem. pg. 2464-2469). It was shown that, under reflux, In(III) salts are capable of catalyzing hydrothiolation reactions between thioacetic acid and a variety of alkenes in a Markovnikov fashion (Weïwer & Duñach (2006) supra). Addition of thiols and thioacids to non-activated olefins by AlIII and InIII have also been described (Coulombel, et al. (2008) Chem. Biodiver. 5:1070-1082).
WO 2007/007084 further teaches a process for the addition of a nucleophile such as an acid, alcohol, amine or thiol, to an alkene using the transition metal copper (II) as catalyst. While this reference demonstrates the use of Cu(OTF)2 in combination with oxygen and nitrogen nucleophiles, hydrothiolation reactions using Cu(OTf)2 were not demonstrated.